Acanthamoeba keratitis is a sight-threatening disease that is caused by Invasion of the eye by a free-living amoeba of the genus Acanthamoeba. Since its initial description in 1973, the incidence of Acanthamoeba keratitis has steadily increased. In spite of significant improvement in the diagnosis of Acanthamoeba keratitis, progress in developing and utilizing effective antimicrobial agents for treating this disease have been disappointing. Moreover, the emergence of drug resistance poses a serious problem in the management of Acanthamoeba infections. The long range goal of the present project is to develop effective strategies for preventing and treating Acanthamoeba keratitis. A growing body of evidence suggests that the mammalian immune system, if properly activated, is capable of preventing and controlling ocular Acanthamoeba infections as well as infections produced by other microorganisms. Therefore, a secondary and equally Important, long range goal of this project is to gain a better understanding of the immune effector mechanisms that protect the cornea from infectious agents. In order to develop effective immunotherapeutic modalities, it is necessary to fully characterize and evaluate the immunobiology of Acanthamoeba keratitis. The present application seeks to characterize and evaluate the immunobiology of experimental Acanthamoeba keratitis in a Chinese hamster model of this disease. Three specific aims will be addressed. The first specific aim will characterize the protective immunity to Acanthamoeba keratitis that is induced by oral and topical administration of Acanthamoeba antigens. The second specific aim will characterize the systemic and local ocular immune responses that are induced by corneal infections in Chinese hamsters. Preliminary studies indicate that the presence of Langerhans cells in corneas exposed to Acanthamoeba-laden contact lenses prevents the development of Acanthamoeba keratitis. Therefore, the third specific aim will evaluate the role of corneal Langerhans cells in the resistance to Acanthamoeba keratitis.